Collagen is widely accepted as having suitable biological properties for use as a biomaterial and has been used in a variety of surgical applications. Such applications include bioprosthetic heart valves, tendon prostheses, vascular grafts and wound repair. In some cases, the collagen is biodegradable and is ultimately completely replaced by natural tissue, in others the collagen has been treated to render it essentially non-degradable.
The use of calcium phosphate ceramics in hard tissue repair and replacement has been investigated extensively for a number of years. These ceramics are available in a number of compositions; hydroxyapatite, modified hydroxyapatite and a hydroxyapatite-tricalcium phosphate composite. Both porous and fully dense ceramics are in use. These materials show excellent biocompatibility, exhibiting good bone bonding and osteoconductivity, but are unsuitable for use in load bearing sites as the mechanical properties, especially the fatigue strength, are inadequate.
Bone is a composite of calcium phosphate with collagen, and the interaction of the hard brittle ceramic phase and the pliant organic matrix give bone its unique mechanical properties. Thus a logical step in the development of the ideal bone substitute is to mimic the structure of bone and mix collagen and calcium phosphate. Such composites have been produced by mixing calcium phosphate granules with a collagen web or mixing calcium phosphate particles with a collagen suspension. More recently, methods have focused on the precipitation of calcium phosphate onto a preformed collagen matrix.
A diffusion based method has been used to precipitate octacalcium phosphate onto rat tail collagen discs. Another author precipitated hydroxyapatite onto collagen by enclosing collagen fibrils in a semipermeable cellulose membrane and allowing ions to diffuse through the cellulose-collagen assembly. In this case the cellulose membrane was controlling the diffusion of the ions and the collagen was suspended in a calcium phosphate solution.
However, materials prepared in this way are limited in the extent to which they can match the properties of bone, because mineral nucleation in the natural material occurs not only on the surface of the fibres, but within the collagen fibrils. To force the precipitation of calcium phosphate inside collagen fibrils the inventors have developed a diffusion based method, in which the calcium and phosphate ions migrate into the collagen matrix from opposite sides and precipitate where they meet: inside the collagen membrane. They have precipitated hydroxyapatite on and within a collagen sheet, using the collagen membrane to separate reservoirs of calcium and phosphate ions. The relative concentrations of the two ions have been adjusted to ensure precipitation occurs inside the membrane.
In one aspect the invention provides a method of making a composite material suitable for use as artificial bone, which method comprises providing a membrane of a biocompatible hydrophilic organic polymer, a solution of calcium ions adjacent a first surface of the membrane, a solution of phosphate ions adjacent a second surface of the membrane, and causing calcium ions and phosphate ions diffusing through the membrane to meet and precipitate as a hydroxyapatite material.
In another aspect the invention provides a composite material suitable for use as artificial bone, comprising a matrix of a biocompatible hydrophilic organic polymer and a hydroxyapatite material deposited within the matrix.
In another aspect the invention provides a composite material suitable for use as artificial bone, comprising a membrane of a biocompatible hydrophilic organic polymer and a hydroxyapatite material deposited within the membrane, or a product formed by pressing into a desired shape the said membrane.